A larger percentage of African Americans than Americans of European ancestry have Alzheimer's disease (AD). The underlying causes of this health disparity are not well understood. African American seniors perform worse than white seniors on a range of cognitive tests. Differences in socioeconomic and health status account for large portions of this disparity, but differences remain. Although race has no biological basis, discrimination related to racial minority status is a salient chronic psychosocial stressor in African Americans that has negative health consequences, contributing to obesity, hypertension, and other conditions. This suggests that psychosocial chronic stress due to experiences of racism may contribute to the health disparities in AD and cognition. The hippocampus is a brain area critical for learning and memory that, together with the entorhinal cortex, is negatively impacted by both AD and chronic stress. Stress models have shown that the rate of adult neurogenesis in the hippocampus, which is the generation of new neurons in the adult brain, is negatively affected by chronic stress, aging, and AD. In addition, the hippocampus and entorhinal cortex have a high concentration of glucocorticoid receptors, which are binding sites for the ?stress hormone? cortisol. Another well-established modulator of adult neurogenesis is aerobic exercise. Aerobic exercise and chronic stress are both potent, but opposite modulators of adult neurogenesis. Increasing physical activity is one of the most effective interventions for slowing down cognitive decline in aging and AD. The goal of this research is to examine how psycho-social chronic stress due to experiences of racism affects the hippocampal memory system (Aim 1), and to examine an association between moderate-intensity physical activity and hippocampal function and structure (Aim 2A) comparing African American seniors with those of European ancestry. We will then investigate whether cortisol, measured in saliva, mediates, i.e. explains, the association between chronic stress and brain integrity, and whether moderate-intensity physical activity and race moderate the strength of the correlation between chronic stress and integrity of the hippocampus and of cortical regions known to be affected by AD (Aim 2B). We will address these questions with high-resolution functional and structural MRI to examine brain integrity. These neuroimaging techniques have the resolution to zoom in on the dentate gyrus subfield of the hippocampus, which is the primary area where adult neurogenesis occurs, while at the same time allowing examination of cortical AD signature regions. We will leverage the availability of an African American cohort in the Health Outreach Program for the Elderly (HOPE) registry at the Boston University Alzheimer's Disease Center. The proposed work could generate a new hypothesis: individuals experiencing chronic psychosocial stress due to racism may show accelerated cognitive decline consistent with AD. In the future this new hypothesis could then be tested by following HOPE participants longitudinally and could examine exercise training as a modulator. Reducing the AD health disparity among racial/ethnic groups in the U.S. is a critical public health goal.